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Alanine transaminase

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Alanine transaminase (ALT), also known as alanine aminotransferase (ALT or ALAT), formerly serum glutamate-pyruvate transaminase (GPT) or serum glutamic-pyruvic transaminase (SGPT), is a transaminase enzyme (EC 2.6.1.2) that was first characterized in the mid-1950s by Arthur Karmen and colleagues.[1] ALT is found in plasma and in various body tissues but is most common in the liver. It catalyzes the two parts of the alanine cycle. Serum ALT level, serum AST (aspartate transaminase) level, and their ratio (AST/ALT ratio) are routinely measured clinically as biomarkers for liver health.[2]

Alanine transaminase
Human alanine transaminase 2 homodimer bound to PLP. PDB: 3IHJ​
Identifiers
EC no.2.6.1.2
CAS no.9000-86-6
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MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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The half-life of ALT in the circulation approximates 47 hours.[3] Aminotransferase is cleared by sinusoidal cells in the liver.[3]

Function

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ALT catalyzes the transfer of an amino group from L-alanine to α-ketoglutarate, the products of this reversible transamination reaction being pyruvate and L-glutamate.[4]

L-alanine + α-ketoglutarate ⇌ pyruvate + L-glutamate
 

ALT (and all aminotransferases) require the coenzyme pyridoxal phosphate, which is converted into pyridoxamine in the first phase of the reaction, when an amino acid is converted into a keto acid.[5]

Further information: Prati criteria

Clinical significance

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ALT is commonly measured clinically as part of liver function tests and is a component of the AST/ALT ratio.[6] When used in diagnostics, it is almost always measured in international units/liter (IU/L)[7] or μkat. While sources vary on specific reference range values for patients, 0-40 IU/L is the standard reference range for experimental studies.[6]

Elevated levels

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Test results should always be interpreted using the reference range from the laboratory that produced the result. However typical reference intervals for ALT are:

Patient type Reference ranges[8]
Male ≤ 45 IU/L
Female ≤ 34 IU/L

Significantly elevated levels of ALT (SGPT) often suggest the existence of other medical problems such as viral hepatitis, diabetes, congestive heart failure, liver damage, bile duct problems, infectious mononucleosis, or myopathy, so ALT is commonly used as a way of screening for liver problems.[citation needed] Elevated ALT may also be caused by dietary choline deficiency.[citation needed] However, elevated levels of ALT do not automatically mean that medical problems exist. Fluctuation of ALT levels is normal over the course of the day, and they can also increase in response to strenuous physical exercise.[9]

When elevated ALT levels are found in the blood, the possible underlying causes can be further narrowed down by measuring other enzymes. For example, elevated ALT levels due to hepatocyte damage can be distinguished from bile duct problems by measuring alkaline phosphatase. Also, myopathy-related elevations in ALT should be suspected when the aspartate transaminase (AST) is greater than ALT; the possibility of muscle disease causing elevations in liver tests can be further explored by measuring muscle enzymes, including creatine kinase. Many drugs may elevate ALT levels, including zileuton, omega−3-acid ethyl esters (Lovaza),[10] anti-inflammatory drugs, antibiotics, cholesterol medications, some antipsychotics such as risperidone, and anticonvulsants.[11] Paracetamol (acetaminophen) may also elevate ALT levels.[12]

For years, the American Red Cross used ALT testing as part of the battery of tests to ensure the safety of its blood supply by deferring donors with elevated ALT levels. The intent was to identify donors potentially infected with hepatitis C because no specific test for that disease was available at the time. Prior to July 1992, widespread blood donation testing in the US for hepatitis C was not carried out by major blood banks. With the introduction of second-generation ELISA antibody tests for hepatitis C, the Red Cross changed the ALT policy. As of July 2003, donors previously disqualified for elevated ALT levels and no other reason may be reinstated as donors when they contact the donor-counseling department of their regional Red Cross organization.[13]

In 2000, the American Association for Clinical Chemistry determined that the appropriate terminology for AST and ALT are aspartate aminotransferase and alanine aminotransferase. The term transaminase is outdated and no longer used in liver disease.[14]

Low ALT

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Low plasma ALT can be a marker of low muscle mass and is associated with frailty, sarcopenia, disability, as well as increased mortality in the elderly population.[15] In patients with inflammatory bowel disease, low ALT is associated with a more active disease.[16]

See also

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References

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  1. ^ Karmen A, Wroblewski F, Ladue JS (January 1955). "Transaminase activity in human blood". The Journal of Clinical Investigation. 34 (1): 126–31. doi:10.1172/JCI103055. PMC 438594. PMID 13221663.
  2. ^ Djakpo, Dodji Kossi; Wang, Zhi Quan; Shrestha, Merina (26 December 2020). "The significance of transaminase ratio (AST/ALT) in acute myocardial infarction". Archives of Medical Science – Atherosclerotic Diseases. 5 (1): 279–283. doi:10.5114/amsad.2020.103028. ISSN 2451-0629. PMC 7885810.
  3. ^ a b Giannini EG, Testa R, Savarino V (February 2005). "Liver enzyme alteration: a guide for clinicians". Canadian Medical Association Journal. 172 (3): 367–79. doi:10.1503/cmaj.1040752. PMC 545762. PMID 15684121. Aminotransferase clearance is carried out within the liver by sinusoidal cells. The half-life in the circulation is about 47 hours for ALT, about 17 hours for total AST and, on average, 87 hours for mitochondrial AST.
  4. ^ Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L, Gong DW (February 2009). "Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity". Hepatology. 49 (2): 598–607. doi:10.1002/hep.22657. PMC 2917112. PMID 19085960.
  5. ^ Vroon, David H.; Israili, Zafar (1990), Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.), "Aminotransferases", Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.), Boston: Butterworths, ISBN 978-0-409-90077-4, PMID 21250265, retrieved 29 July 2024
  6. ^ a b Lala V, Goyal A, Bansal P, Minter D (July 2020). "Liver Function Tests". Stat Pearls. Treasure Island (FL): StatPearls Publishing. PMID 29494096.
  7. ^ Ghouri N, Preiss D, Sattar N (September 2010). "Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data". Hepatology. 52 (3): 1156–61. doi:10.1002/hep.23789. PMID 20658466. S2CID 5141849.
  8. ^ Marshall W (2012). "Alanine aminotransferase: analyte monograph" (PDF). Association for Clinical Biochemistry and Laboratory Medicine. pp. 3–7. Archived from the original (PDF) on 8 August 2014. Retrieved 7 October 2013.
  9. ^ Giboney PT (March 2005). "Mildly elevated liver transaminase levels in the asymptomatic patient". American Family Physician. 71 (6): 1105–10. PMID 15791889.
  10. ^ Dubbeldam JL, de Jongh HJ, Osse JW (2008). "Pieter Dullemeijer, professor of animal morphology". Acta Morphologica Neerlando-Scandinavica. 27 (1–2): 9–16. PMID 2683599.
  11. ^ Bays, Harold E.; McKenney, James; Maki, Kevin C.; Doyle, Ralph T.; Carter, Roderick N.; Stein, Evan (1 February 2010). "Effects of Prescription Omega-3-Acid Ethyl Esters on Non—High-Density Lipoprotein Cholesterol When Coadministered With Escalating Doses of Atorvastatin". Mayo Clinic Proceedings. 85 (2): 122–128. doi:10.4065/mcp.2009.0397. PMC 2813819.
  12. ^ Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC (July 2006). "Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial". JAMA. 296 (1): 87–93. doi:10.1001/jama.296.1.87. PMID 16820551.
  13. ^ Van Ostrand D. "Red Cross Donor Requirements". American Red Cross of Tompkins County. Archived from the original on 3 November 2005. Retrieved 1 August 2005.
  14. ^ Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB (December 2000). "Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests". Clinical Chemistry. 46 (12): 2027–49. doi:10.1093/clinchem/46.12.2027. PMID 11106349.
  15. ^ Vespasiani-Gentilucci, Umberto; De Vincentis, Antonio; Ferrucci, Luigi; Bandinelli, Stefania; Incalzi, Raffaele Antonelli; Picardi, Antonio (17 June 2017). "Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival". The Journals of Gerontology. 73 (7): 925–930. doi:10.1093/gerona/glx126. PMC 6001897. PMID 28633440. Retrieved 24 March 2024.
  16. ^ Shafrir, Asher; Katz, Lior H.; Shauly-Aharonov, Michal; Zinger, Adar; Safadi, Rifaat; Stokar, Joshua; Kalisky, Itay (24 March 2024). "Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study". Journal of Clinical Medicine. 13 (7): 1869. doi:10.3390/jcm13071869. ISSN 2077-0383. PMC 11012492.
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